Abnormal red blood cell (RBC) function, particularly decreased cell deformability, has been documented in[unreadable] sepsis, after trauma and during shock states. This decrease in RBC deformability is associated with, and[unreadable] has been shown to directly cause, impaired nutrient blood flow to various tissues, and thus might[unreadable] contribute to the development of the multiple organ dysfunction syndrome (MODS). However, the exact[unreadable] mechanisms and factors that lead to decreased RBC deformability remain to be determined. There are[unreadable] also studies that have documented more normal RBC deformability in women with cardiovascular disease[unreadable] than is seen in men with similar disease. We therefore wish to test the following two hypotheses: (1) that[unreadable] decreased RBC deformability after trauma-hemorrhage shock (T/HS) is secondary to gut injury and is[unreadable] mediated by factors carried in the intestinal lymph and; (2) that the changes in deformability following T/HS[unreadable] are less in females than in males. We will test the first hypothesis and investigate[unreadable] mechanisms by which toxic mesenteric lymph injures red cells. We propose to[unreadable] investigate the role of sex hormones as modulators of T/HS-induced RBC deformability in vivo. This is[unreadable] based on our pilot studies showing that female rats are more resistant to T/HS-induced changes in RBC[unreadable] deformability than male rats, as well as human studies indicating that RBC deformability is better[unreadable] preserved in pre-menopausal than post-menopausal women. Using in vitro studies, we[unreadable] propose to investigate the potential mechanisms responsible for the resistance of female rats to T/HS[unreadable] focusing on the role of sex hormones. Lastly, we propose to expand these animal[unreadable] studies to include male and female trauma patients. We believe these clinical studies will be important[unreadable] since they will allow us to compare the results observed in our T/HS model with those observed in trauma[unreadable] patients.